Fig. 8

Light-dependent photoreceptor degeneration in E168d2neo/+ mice. a Heatmap presents P21 Crx mutant FC relative to WT for genes involved in the photoreceptor visual cycle. b Model for the RPE visual cycle: visual chromophore [11-cis-retinal (RAL)] is generated in the retinal pigmented epithelium (RPE) and delivered to the photoreceptor; stimulation of 11-cis RAL bound to an opsin protein activates the phototransduction cascade leading to photoreceptor membrane hyperpolarization; this process isomerizes 11-cis RAL into all-trans RAL, which is then recycled back into 11-cis-RAL through a series of enzymatic steps, known as the visual cycle, in the photoreceptor and RPE. The drug 13-cis retinoic acid (13-cis-RA) blocks the synthesis of 11-cis-RAL, effectively reducing the burden on the retinoid cycle. ROL retinol. c, d Retinal morphology of 6-week-old mice with indicated genotypes under normal light conditions: 12 h room light–dark cycle (c) or light damage (LD) treatments (8 h 11.5–13.5 KLUX bright light followed by 7 days of normal light–dark cycles) (d). Retinal morphology was assessed by hematoxylin and eosin (H&E) staining of sagittal retinal sections through the optic nerve (ON). Images were taken in the central superior retina (~500 μm from the ON). e Morphometry quantification of ONL thickness for the samples presented in (c, d). Error bars represent standard error of mean (SE) from three or more biological replicates and significance was calculated using two-way ANOVA. Data points that significantly differ from the control (p ≤ 0.05) are marked by red asterisks. f, g Effect of 13-cis retinoic acid (13-cis-RA) pretreatment on LD in E168d2neo/+ mutant mice: retinal morphology (f) and morphometry (g) at 7 days following LD where mice were pretreated with 13-cis-RA or dimethyl sulfoxide (DMSO) as control. Note the significant improvements in ONL thickness and photoreceptor outer segment (OS) length in the mice treated with 13-cis-RA. GCL ganglion cell layer, INL inner nuclear layer, IPL inner plexiform layer, ONL outer nuclear layer, OPL outer plexiform layer, OS outer segment. Scale bar = 50 μm